title: The frequency of α₄β₇(high) memory CD4⁺ T cells correlates with susceptibility to rectal simian immunodeficiency virus infection.
abstract: BACKGROUND
  Integrin α₄β₇(high) (α₄β₇(high)) mediates the homing of CD4⁺ T cells to gut-associated lymphoid tissues, which constitute a highly favorable environment for HIV expansion and dissemination. HIV and simian immunodeficiency virus (SIV) envelope proteins bind to and signal through α₄β₇(high) and during acute infection SIV preferentially infects α₄β₇(high) CD4⁺ T cells. We postulated that the availability of these cells at the time of challenge could influence mucosal SIV transmission and acute viral load (VL).
  
  
  METHODS
  We challenged 17 rhesus macaques with 3000 TCID50 of SIVmac239 rectally and followed the subsets of α₄β₇(high) T cells and dendritic cells (DCs) by flow cytometry in blood and tissues, before and after challenge.
  
  
  RESULTS
  We found that the frequency of memory CD4⁺ T cells that expressed high levels of α₄β₇(high) (α₄β₇(high) memory CD4⁺ T cells) in blood before challenge correlated strongly with susceptibility to infection and acute VL. Notably, not only at the time of challenge but also their frequency 3 weeks before challenge correlated with infection. This association extended to the rectal tissue as we observed a strong direct correlation between the frequency of α₄β₇(high) memory CD4⁺ T cells in blood and rectum before and after challenge. The frequency of α4β7 myeloid DCs and α₄β₇(high) CD80⁺ DCs also correlated with infection and acute VL, whereas blood CCR5⁺ and CD69⁺ CD4⁺ T cells could not be associated with infection.
  
  
  CONCLUSIONS
  Our results suggest that animals with higher frequency of α₄β₇(high) CD4⁺ T cells in circulation and in rectal tissue could be more susceptible to SIV rectal transmission.
authors.affiliation: *Center for Biomedical Research, Population Council, New York, NY; †Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD; ‡AIDS and Cancer Virus Program, SAIC-Frederick, Inc., National Cancer Institute, Frederick, MD; §Tulane National Primate Research Center, Tulane University Sciences Center, Covington, LA; and ‖Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY.
authors.forename: Elena
authors.initials: E
authors.lastname: Martinelli
authors.forename: Filippo
authors.initials: F
authors.lastname: Veglia
authors.forename: Diana
authors.initials: D
authors.lastname: Goode
authors.forename: Natalia
authors.initials: N
authors.lastname: Guerra-Perez
authors.forename: Meropi
authors.initials: M
authors.lastname: Aravantinou
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Melissa
authors.initials: M
authors.lastname: Robbiani
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000145:classification* / Q000502:physiology*; D004198:Disease Susceptibility; D005434:Flow Cytometry; D007156:Immunologic Memory / Q000502:physiology; D016023:Integrins / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D012007:Rectum; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus
chemical_list: D016023:Integrins